ReviewCrimean–Congo hemorrhagic fever
Section snippets
Early history of Crimean–Congo hemorrhagic fever (CCHF)
A disease now considered to be CCHF was described by a physician in the 12th century from the region that is presently Tadzhikistan. The description was of a hemorrhagic disease with the presence of blood in the urine, rectum, gums, vomitus, sputum, and abdominal cavity and was said to be caused by a louse or tick, which normally parasitizes a blackbird (Hoogstraal, 1979). The arthropod described may well have been a species of Hyalomma tick larvae which are frequently found on blackbirds. CCHF
Classification of the virus
CCHFV is a member of the Nairovirus genus of the family Bunyaviridae. Other genera within the family include Orthobunyavirus, Hantavirus, Phlebovirus, and Tospovirus. According to the most recent report from the International Committee on the Taxonomy of Viruses, there are seven recognized species in the genus Nairovirus containing 34 viral strains (Elliott et al., 2000), all of which are believed to be transmitted by either ixodid or argasid ticks (i.e., hard or soft ticks, respectively). The
Structure and molecular biology of the virus
Relatively few studies have been made on the structure of CCHFV. Murphy et al., 1968, Murphy et al., 1973 first described the morphology of CCHFV in the brains of infected newborn mice and noted the similarity to members of the Bunyaviridae family. Indeed, it is now known that CCHFV, and nairoviruses in general, are typical of other members of the family Bunyaviridae in terms of their basic structure, morphogenesis, replication cycle, and physicochemical properties (Donets et al., 1977, Ellis
Strain variation and phylogenetic relationships
Many early studies, based on serological testing, suggested that there are very few significant differences among strains of CCHFV. For example, studies employing modified agar gel diffusion precipitation, neutralization, cell culture interference, and complement fixation tests demonstrated that there were no apparent antigenic differences among strains from several different geographic locations in the former Soviet Union and Africa (Casals, 1969, Casals et al., 1970, Chumakov et al., 1969,
Vertebrate reservoir hosts
Like other tick-borne zoonotic agents, CCHFV generally circulates in nature unnoticed in an enzootic tick–vertebrate–tick cycle. CCHFV has been isolated from numerous domestic and wild vertebrates, including cattle and goats (Woodall et al., 1965, Causey et al., 1970), sheep (Yu-Chen et al., 1985), hares (Chumakov, 1974), hedgehogs (Causey et al., 1970), a Mastomys spp. mouse (Saluzzo et al., 1985), and even domestic dogs (Shepherd et al., 1987a, Shepherd et al., 1987b). Sera from several
Clinical features
Humans appear to be the only host of CCHFV in which disease is manifested (except for newborn mice). In contrast to the inapparent infection in most other vertebrate hosts, human infection with CCHFV often results in severe hemorrhagic disease. The historical accounts of disease attributed to CCHF have been reviewed in detail by Hoogstraal (1979). The typical course of CCHF has been noted by some authors as progressing through four distinct phases, i.e., incubation, prehemorrhagic, hemorrhagic,
Pathogenesis/clinical pathology
The pathogenesis of CCHF is poorly understood. Because CCHF occurs sporadically, and in areas where clinical pathology facilities are limited, complete autopsies are seldom performed on patients who die from the disease. Additional factors that hamper studies on CCHF include the need for specialized laboratories (i.e., biosafety level-4 (BSL-4) containment) and lack of available animal models of disease. Therefore, limited knowledge of pathogenesis is often obtained from blood changes and liver
Diagnosis
Early diagnosis is essential, both for the outcome of the patient and, because of the potential for nosocomial infections, to prevent further transmission of disease. Clinical symptoms and patient history, especially travel to endemic areas and history of tick bite or exposure to blood or tissues of livestock or human patients, are the first indicators of CCHF. The differential diagnosis should include rickettsiosis (tick-borne typhus and African tick bite fever), leptospirosis, and borreliosis
Treatment
Treatment options for CCHF are limited. Early remedies included giving rutin (a bioflavonoid compound found in buckwheat), ascorbic acid, and calcium chloride for the treatment of the hemorrhagic syndrome. It was also suggested that with extensive blood loss, transfusions and blood substitutes such as polyglutin, plasma, and hemodes were necessary and intravenous injections of gelatin and aminocaproic acid were also indicated. Much emphasis was also placed on preventing reinfection, including
Risk factors
There are several groups of individuals who are considered to be at-risk of contracting CCHFV. Specifically, people from endemic areas who are susceptible to tick bite, particularly from Hyalomma spp. ticks. These would include individuals who work outdoors, particularly those who work with large domestic animals. Although CCHFV has been isolated from numerous species of ticks (see Section 5), those of the Hyalomma genus are considered the primary vector in CCHF enzootic and endemic areas. The
Potential bioterrorism concerns
The highly pathogenic nature of the CCHFV has led to the fear that it might be used as an agent of bioterrorism and/or biowarfare and has resulted in its inclusion as a CDC/NIAID Category C Priority Pathogen. CCHFV can be transmitted from person to person, has a high case-fatality rate, and may be transmissible by small-particle aerosol; but, its inability to replicate to high concentrations in cell culture is cited as a major impediment to its development as a mass casualty weapon (Borio et
Acknowledgements
I thank Mike Bray (NIH) for many useful discussions regarding this work. I also thank Katheryn Kenyon (USAMRIID), Aysegul Nalca (Southern Research Institute), and Mike Bray (NIH) for critically reading the manuscript and providing useful editorial suggestions. Many thanks go to Christopher Mores (University of Florida) for helpful discussions regarding phylogenetic analyses and to Connie Schmaljohn (USAMRIID) for supplying Fig. 1, Fig. 2. Additionally, the author is indebted to members of the
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The views, opinions, and findings contained herein are those of the author and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation.